tbuckley/cabot-search huggingface dataset:
Radiomics and Deep Learning in Nasopharyngeal Carcinoma: A Review
Authors: Zipei Wang, Mengjie Fang, Jie Zhang, Linquan Tang, Lianzhen Zhong, Hailin Li, Runnan Cao, Xun Zhao, Shengyuan Liu, Ruofan Zhang, Xuebin Xie, Haiqiang Mai, Sufang Qiu, Jie Tian, Di Dong
Journal: IEEE Reviews in Biomedical Engineering (2023)

Nasopharyngeal carcinoma is a common head and neck malignancy with distinct clinical management compared to other types of cancer. Precision risk stratification and tailored therapeutic interventions are crucial to improving the survival outcomes. Artificial intelligence, including radiomics and deep learning, has exhibited considerable efficacy in various clinical tasks for nasopharyngeal carcinoma. These techniques leverage medical images and other clinical data to optimize clinical workflow and ultimately benefit patients. In this review, we provide an overview of the technical aspects and basic workflow of radiomics and deep learning in medical image analysis. We then conduct a detailed review of their applications to seven typical tasks in the clinical diagnosis and treatment of nasopharyngeal carcinoma, covering various aspects of image synthesis, lesion segmentation, diagnosis, and prognosis. The innovation and application effects of cutting-edge research are summarized. Recognizing the heterogeneity of the research field and the existing gap between research and clinical translation, potential avenues for improvement are discussed. We propose that these issues can be gradually addressed by establishing standardized large datasets, exploring the biological characteristics of features, and technological upgrades.
Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated <i>KRAS</i> G12C-Mutated Non–Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100
Authors: Grace K. Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S. Falchook, Antoine Italiano, Jürgen Wolf, Adrian G. Sacher, Toshiaki Takahashi, Suresh S. Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, David S. Hong, Piro Lito, Qui Tran, Simon Jones, Abraham Anderson, Antreas Hindoyan, Wendy Snyder, Ferdinandos Skoulidis, Bob T. Li
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the longest follow-up, to our knowledge, for a KRASG12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non-small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials.gov identifier: NCT03600883). This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies. Patients (N = 174) received sotorasib 960 mg once daily with the primary end points for phase I of safety and tolerability and for phase II of objective response rate (ORR). Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 months, and 2-year OS rate of 33%. Long-term clinical benefit (PFS ≥ 12 months) was observed in 40 (23%) patients across PD-L1 expression levels, in a proportion of patients with somatic STK11 and/or KEAP1 alterations, and was associated with lower baseline circulating tumor DNA levels. Sotorasib was well tolerated, with few late-onset treatment-related toxicities, none of which led to treatment discontinuation. These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis.
The Clinicogenomic Landscape of Induction Failure in Childhood and Young Adult T-Cell Acute Lymphoblastic Leukemia
Authors: David O'Connor, Jonas Demeulemeester, Lucia Conde, Amy Kirkwood, Kent Fung, Foteini Papaleonidopoulou, Gianna Bloye, Nadine Farah, Sunniyat Rahman, Jeremy Hancock, Caroline Bateman, Sarah Inglott, Jon Mee, Javier Herrero, Peter Van Loo, Anthony V. Moorman, Ajay Vora, Marc R. Mansour
Journal: Journal of Clinical Oncology (2023)

Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).
Heterogeneity of reported outcomes in epidermolysis bullosa clinical research: a scoping review as a first step towards outcome harmonization
Authors: Eva W H Korte, Tobias Welponer, Jan Kottner, Sjoukje van der Werf, Peter C van den Akker, Barbara Horváth, Dimitra Kiritsi, Martin Laimer, Anna M G Pasmooij, Verena Wally, Maria C Bolling
Journal: British Journal of Dermatology (2023)

Abstract Background Epidermolysis bullosa (EB) is a rare, genetically and clinically heterogeneous group of skin fragility disorders. No cure is currently available, but many novel and repurposed treatments are upcoming. For adequate evaluation and comparison of clinical studies in EB, well-defined and consistent consensus-endorsed outcomes and outcome measurement instruments are necessary. Objectives To identify previously reported outcomes in EB clinical research, group these outcomes by outcome domains and areas and summarize respective outcome measurement instruments. Methods A systematic literature search was performed in the databases MEDLINE, Embase, Scopus, Cochrane CENTRAL, CINAHL, PsycINFO and trial registries covering the period between January 1991 and September 2021. Studies were included if they evaluated a treatment in a minimum of three patients with EB. Two reviewers independently performed the study selection and data extraction. All identified outcomes and their respective instruments were mapped onto overarching outcome domains. The outcome domains were stratified according to subgroups of EB type, age group, intervention, decade and phase of clinical trial. Results The included studies (n = 207) covered a range of study designs and geographical settings. A total of 1280 outcomes were extracted verbatim and inductively mapped onto 80 outcome domains and 14 outcome areas. We found a steady increase in the number of published clinical trials and outcomes reported over the past 30 years. The included studies mainly focused on recessive dystrophic EB (43%). Wound healing was reported most frequently across all studies and referred to as a primary outcome in 31% of trials. Great heterogeneity of reported outcomes was observed within all stratified subgroups. Moreover, a diverse range of outcome measurement instruments (n = 200) was identified. Conclusions We show substantial heterogeneity in reported outcomes and outcome measurement instruments in EB clinical research over the past 30 years. This review is the first step towards harmonization of outcomes in EB, which is necessary to expedite the clinical translation of novel treatments for patients with EB.
Peptide-mediated delivery of CRISPR enzymes for the efficient editing of primary human lymphocytes
Authors: Dana V. Foss, Joseph J. Muldoon, David N. Nguyen, Daniel Carr, Srishti U. Sahu, John M. Hunsinger, Stacia K. Wyman, Netravathi Krishnappa, Rima Mendonsa, Elaine V. Schanzer, Brian R. Shy, Vivasvan S. Vykunta, Vincent Allain, Zhongmei Li, Alexander Marson, Justin Eyquem, Ross C. Wilson
Journal: Nature Biomedical Engineering (2023)
Intraoperative Radiation Therapy
Authors: Christopher G. Willett, Brian G. Czito, Douglas S. Tyler
Journal: Journal of Clinical Oncology (2007)

Intraoperative radiation therapy (IORT) is the delivery of irradiation at the time of an operation. This is performed by different techniques including intraoperative electron beam techniques and high-dose rate brachytherapy. IORT is usually given in combination with external-beam radiation therapy with or without chemotherapy and surgical resection. IORT excludes part or all dose-limiting sensitive structures, thereby increasing the effective dose to the tumor bed (and therefore local control) without significantly increasing normal tissue morbidity. Despite best contemporary therapy, high rates of local failure occur in patients with locally advanced or recurrent rectal cancer, retroperitoneal sarcoma, select gynecologic cancers, and other malignancies. The addition of IORT to conventional treatment methods has improved local control as well as survival in many disease sites in both the primary and locally recurrent disease settings. More recently, there has been interest in the use of IORT as a technique of partial breast irradiation for women with early breast cancer. Given newer and lower cost treatment devices, the use of IORT in clinical practice will likely grow, with increasing integration into the treatment of nonconventional malignancies. Optimally, phase III randomized trials will be carried out to prove its efficacy in these disease sites.
Abstract 10180: Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT Trial
Authors: Sitong Li, Chao Jiang, Yufeng Wang, Yiwei Lai, liu HE, Ribo Tang, Chen-Xi Jiang, Caihua Sang, Deyong Long, Xin Du, jz Dong, Changsheng Ma
Journal: Circulation (2022)

Introduction: Systolic blood pressure (SBP) time in target range (TTR) was proven to be a new parameter to predict cardiovascular outcomes. However, the prognostic value for cognitive function is unclear. Hypothesis: Higher TTR was associated with lower incidence of cognitive outcomes. Methods: We performed a post hoc analysis from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized controlled trial comparing intensive (&lt;120 mm Hg) and standard (&lt;140 mm Hg) SBP interventions in 9361 individuals with hypertension. SBP target range was defined as 110 to 130 mm Hg for the intensive group and 120 to 140 mm Hg for the standard group. Participants who had less than 3 SBP measurements during this period or no cognitive assessment in the follow-up were excluded. TTR was calculated by linear interpolation using SBP from baseline to the first 3 months of follow-up. Cognitive outcomes were probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models were used to evaluate the relationship between TTR and cognitive outcomes. Results: A total of 8415 patients were included in this study. In univariate Cox regression analysis, higher time in target range was associated with lower risk of probable dementia. After adjustment for age, sex and race, a 1-SD increase in TTR was independently associated with a 16% lower risk of probable dementia (hazard ratio [HR] =0.84, 95% CI 0.75-0.93, P =0.002) (Figure). When we further added demographics, medical history and mean SBP to the multivariate Cox regression model, TTR remained significantly associated with a decreased risk of probable dementia (HR =0.84, 95% CI 0.74-0.96, P =0.012). No significant relationship was found between TTR and MCI or a composite of probable dementia or MCI. Conclusions: In this post hoc analysis of the SPRINT trial, SBP time in target range was an independent predictor of probable dementia beyond mean SBP levels.
Abstract 9361: Interleukin-33 System as Potential Biomarker and Therapeutic Target in Kawasaki Disease
Authors: Seigo Okada, Hiroki Yasudo, Yuji Ohnishi, Chie Matsuguma, Reiji Fukano, Takako Waniishi, Shunji Hasegawa
Journal: Circulation (2022)

Introduction: Kawasaki disease (KD) is an acute, self-limiting, febrile systemic vasculitis of unknown cause associated with the development of coronary artery lesions (CALs) during childhood. Damage-associated molecular patterns (DAMPs) from cell death and oxidative stress have been shown to be involved in the development of KD vasculitis. Interleukin (IL)-33 is released from damaged endothelial cells and acts as DAMPs. Hypothesis: IL-33 and its receptor (ST2) might be involved in KD pathogenesis. Methods: Serum levels of soluble ST2 (sST2) in KD patients were measured before their first therapy. Furthermore, we investigated the impact of IL-33 on human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). Results: Serum levels of sST2 were significantly higher in KD patients with CALs than in those with normal coronary arteries (87.2 [18.4-224.0] ng/mL vs. 31.7 [8,8-290.3] ng/mL, p = 0.017). In vitro , IL-33 upregulated the expression of ST2L and increased production of sST2, IL-6, IL-8, and monocyte chemoattractant protein–1 in HCAECs in a time- and concentration-dependent manner. Notably, compared to isoconcentration of tumor necrosis factor-α (TNF-α), IL-33 significantly increased IL-6 production; 10 ng/mL of IL-33 increased the production of IL-6 by 13-fold compared with that by TNF-α (9.1 ng/mL vs. 0.7 ng/mL, p &lt; 0.05). Moreover, IL-1β increases IL-33 production by HCASMCs in a concentration-dependent manner. Conclusions: The results of the present study suggest that the IL-33/ST2 axis might be involved in the development of KD vasculitis. The IL-33/ST2 axis may be a therapeutic target for the treatment of KD.
Guiding Fibroblast Activation Using an RGD‐Mutated Heparin Binding II Fragment of Fibronectin for Gingival Titanium Integration
Authors: Aina Heras‐Parets, Maria‐Pau Ginebra, Jose Maria Manero, Jordi Guillem‐Marti
Journal: Advanced Healthcare Materials (2023)

Abstract The formation of a biological seal around the neck of titanium (Ti) implants is critical for ensuring integration at the gingival site and for preventing bacterial colonization that may lead to periimplantitis. This process is guided by activated fibroblasts, named myofibroblasts, which secrete extracellular matrix (ECM) proteins and ECM‐degrading enzymes resolving the wound. However, in some cases, Ti is not able to attract and activate fibroblasts to a sufficient extent, which may compromise the success of the implant. Fibronectin (FN) is an ECM component found in wounds that is able to guide soft tissue healing through the adhesion of cells and attraction of growth factors (GFs). However, clinical use of FN functionalized Ti implants is problematic because FN is difficult to obtain, and is sensitive to degradation. Herein, functionalizing Ti with a modified recombinant heparin binding II (HBII) domain of FN, mutated to include an Arg‐Gly‐Asp (RGD) sequence for promoting both fibroblast adhesion and GF attraction, is aimed at. The HBII‐RGD domain is able to stimulate fibroblast adhesion, spreading, proliferation, migration, and activation to a greater extent than the native HBII, reaching values closer to those of full‐length FN suggesting that it might induce the formation of a biological sealing.
Cold snaring for gastric sampling and for colonic adenoma resection: an ecological tip to use a single device for the whole endoscopy procedure
Authors: Mathieu Pioche, Clara Yzet, Raphaelle Grau, Jean-Christophe Saurin, Mikael Mochet, Pierre Lafeuille, Jérôme Rivory
Journal: Endoscopy (2023)

The ecological impact of endoscopy is significant [1] and it is therefore crucial to seek strategies [2] [3] for reducing the number of devices used and therefore the weight of waste generated [4]. Endoscopy procedures frequently involve both upper and lower gastrointestinal procedures, for example, gastric sampling for Helicobacter pylori and metaplasia detection on the one hand and colonoscopy with a high risk of detecting polyps on the other. Gastric sampling commonly involves the use of biopsy forceps. Nowadays, cold snaring is the reference method for removing small polyps (< 10 mm), which are very frequently detected during a screening colonoscopy. It means that two devices are usually used during a combined upper and lower gastrointestinal endoscopy procedure, even though cold snaring can perform gastric sampling adequately, and, in fact, provides larger samples with more tissue for pathologists to analyze.
Toxidrome Recognition and Response
Authors: Gregory R. Ciottone, Dan Longo, Darren Taichman
Journal: New England Journal of Medicine (2023)

In this animated Double Take video from the New England Journal of Medicine, viewers are guided through the recognition of and medical response to a fictional terrorist attack involving chemical warfare agents. Based on a review article published in the Journal (Toxidrome Recognition in Chemical-Weapons Attacks, by G.R. Ciottone, in the April 26, 2018, issue), the video discusses several classes of agents, the clinical presentations of persons exposed to the agents, and antidotes. It also demonstrates how first responders use knowledge of toxidromes and mitigation techniques to deal with this fictional scenario.
Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia
Authors: Inge M. van der Sluis, Paola de Lorenzo, Rishi S. Kotecha, Andishe Attarbaschi, Gabriele Escherich, Karsten Nysom, Jan Stary, Alina Ferster, Benoit Brethon, Franco Locatelli, Martin Schrappe, Peggy E. Scholte-van Houtem, Maria G. Valsecchi, Rob Pieters
Journal: New England Journal of Medicine (2023)

KMT2A-rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with 3-year event-free survival below 40%. Most relapses occur during treatment, with two thirds occurring within 1 year and 90% within 2 years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy. Download a PDF of the Research Summary. We studied the safety and efficacy of blinatumomab, a bispecific T-cell engager molecule targeting CD19, in infants with KMT2A-rearranged ALL. Thirty patients younger than 1 year of age with newly diagnosed KMT2A-rearranged ALL were given the chemotherapy used in the Interfant-06 trial with the addition of one postinduction course of blinatumomab (15 μg per square meter of body-surface area per day; 28-day continuous infusion). The primary end point was clinically relevant toxic effects, defined as any toxic effect that was possibly or definitely attributable to blinatumomab and resulted in permanent discontinuation of blinatumomab or death. Minimal residual disease (MRD) was measured by polymerase chain reaction. Data on adverse events were collected. Outcome data were compared with historical control data from the Interfant-06 trial. The median follow-up was 26.3 months (range, 3.9 to 48.2). All 30 patients received the full course of blinatumomab. No toxic effects meeting the definition of the primary end point occurred. Ten serious adverse events were reported (fever [4 events], infection [4], hypertension [1], and vomiting [1]). The toxic-effects profile was consistent with that reported in older patients. A total of 28 patients (93%) either were MRD-negative (16 patients) or had low levels of MRD (<5×10−4 [i.e., <5 leukemic cells per 10,000 normal cells], 12 patients) after the blinatumomab infusion. All the patients who continued chemotherapy became MRD-negative during further treatment. Two-year disease-free survival was 81.6% in our study (95% confidence interval [CI], 60.8 to 92.0), as compared with 49.4% (95% CI, 42.5 to 56.0) in the Interfant-06 trial; the corresponding values for overall survival were 93.3% (95% CI, 75.9 to 98.3) and 65.8% (95% CI, 58.9 to 71.8). Blinatumomab added to Interfant-06 chemotherapy appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged ALL as compared with historical controls from the Interfant-06 trial. (Funded by the Princess Máxima Center Foundation and others; EudraCT number, 2016-004674-17.) QUICK TAKE VIDEO SUMMARYBlinatumomab in Infant Lymphoblastic Leukemia 02:30
Case 13-2023: A 25-Year-Old Woman with Abdominal Pain and Jerking Movements
Authors: Leigh H. Simmons, Mladen Nisavic, Amy K. Dickey
Journal: New England Journal of Medicine (2023)

A 25-year-old woman with a history of acute intermittent porphyria was admitted with abdominal pain and jerking movements of the arm and leg. Symptoms did not abate with hemin treatment. A diagnosis was made.
<i>TET2</i> -Driver and <i>NLRC4</i> -Passenger Variants in Adult-Onset Autoinflammation
Authors: Ellen De Langhe, Sien Van Loo, Bert Malengier-Devlies, Mieke Metzemaekers, Frederik Staels, Jessica Vandenhaute, Nathalie Berghen, Raf Sciot, Anniek Corveleyn, Olga Tšuiko, Mieke Gouwy, Jan Lenaerts, Patrick Verschueren, Carine H Wouters, Paul Proost, Patrick Matthys, Eric Legius, Rik Schrijvers
Journal: New England Journal of Medicine (2023)
Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers
Authors: Laure F. Pittet, Nicole L. Messina, Francesca Orsini, Cecilia L. Moore, Veronica Abruzzo, Simone Barry, Rhian Bonnici, Marc Bonten, John Campbell, Julio Croda, Margareth Dalcolmo, Kaya Gardiner, Grace Gell, Susie Germano, Adriano Gomes-Silva, Casey Goodall, Amanda Gwee, Tenaya Jamieson, Bruno Jardim, Tobias R. Kollmann, Marcus V.G. Lacerda, Katherine J. Lee, Michaela Lucas, David J. Lynn, Laurens Manning, Helen S. Marshall, Ellie McDonald, Craig F. Munns, Suellen Nicholson, Abby O’Connell, Roberto D. de Oliveira, Susan Perlen, Kirsten P. Perrett, Cristina Prat-Aymerich, Peter C. Richmond, Jesus Rodriguez-Baño, Glauce dos Santos, Patricia V. da Silva, Jia Wei Teo, Paola Villanueva, Adilia Warris, Nicholas J. Wood, Andrew Davidson, Nigel Curtis
Journal: New England Journal of Medicine (2023)

The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19).
Dietary Sodium Restriction in Patients with Heart Failure
Authors: Leslie L. Chang, Jacqueline T. DesJardin, Michelle A. Albert, Justin Ezekowitz, Salim Yusuf
Journal: New England Journal of Medicine (2023)

This feature about a patient with heart failure offers a case vignette accompanied by two essays, one supporting recommendation of a low-sodium diet and the other recommending no sodium restriction.
Blunt traumatic isolated duodenal perforation treated by multimodal endoscopic approach
Authors: Durante Donnarumma, Omar Ksissa, Lorenzo Dioscoridi, Edoardo Forti, Osvaldo Chiara, Luigi Raparelli, Massimiliano Mutignani
Journal: Endoscopy (2023)

Duodenal trauma usually consists of retroperitoneal lesions, which represent a small percentage of abdominal injuries. These injuries are difficult to manage by surgery, so endoscopy can be an useful alternative [1] [2] [3].